Intestinal tumour chemoprevention with the antioxidant lipoic acid stimulates the growth of breast cancer.
OBJECTIVE
Breast and intestinal cancers chemoprevention would significantly impact on cancer care. Hence, we assessed the chemopreventive efficacy of the antioxidant lipoic acid (LA) in mice overexpressing a wild-type Her2/neu, as an animal model of breast cancer, and in APCmin mice for intestinal cancer.


METHODS
Mice were randomised at weaning, and were treated with LA for lifetime. Tumour incidence, growth rate and histopathology were analysed on an individual tumour basis.


RESULTS
LA efficiently chemoprevented tumour appearance in APCmin mice. Strikingly, though, LA doses, that were chemopreventive in APCmin mice (> or = 300 microg/day), increased breast cancer growth in Her2/neu mice. Even in experimental groups, where LA overall reduced tumour risk (80 microg/day), LA consistently stimulated the growth rate of established breast tumours. Breast and colon tumours incidence was unaffected by LA, indicating no significant impact of LA on tumour initiation and no protection from mutations driving tumour progression.


CONCLUSIONS
Stimulation of breast cancer growth and inhibition of intestinal tumours by LA indicate that diverse growth control mechanisms are modulated by LA in different organs. Concern is raised about the use of LA for cancer chemoprevention.
Rossi
Cosmo
C
Animal Care Unit, Consorzio Mario Negri Sud, SM Imbaro (Chieti), Italy.
Di Lena
Annalisa
A
La Sorda
Rossana
R
Lattanzio
Rossano
R
Antolini
Laura
L
Patassini
Cristina
C
Piantelli
Mauro
M
Alberti
Saverio
S
D000704:Analysis of Variance; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000975:Antioxidants / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000473:pathology*; D005260:Female; D007414:Intestinal Neoplasms / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D011897:Random Allocation; D008063:Thioctic Acid / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D000975:Antioxidants; D008063:Thioctic Acid